Simultaneous combined measurement of antikeratin antibody and rheumatoid factor: additive value in the diagnosis of rheumatoid arthritis

Rheumatoid arthritis [RA] is a systemic inflammatory autoimmune disease of unknown etiology characterized by chronic polyarthritis. Its highly variable and unpredictable course is the underlying reason for the search for new and more sensitive and specific laboratory markers. The only serologic test routinely used in RA assessment is the determination of rheumatoid factor [RF] in the serum. Although RF has sensitivity up to 80%, still it lacks specificity. To evaluate a new marker "antikeratin antibody" [AKA] regarding its sensitivity and specificity and its relation to disease activity. Also the combined RF and AKA, does it add to the diagnosis of RA. Sera from 88 consecutive RA patients, 40 disease controls and 50 healthy controls were tested for RF with latex agglutination and AKA with indirect immunofluorescence assay that used rat esophagus as a substrate. The proportion of RA patients who had AKA [49/88] was higher than in healthy controls 4/50 [X[2]=28.6, p<0.001], and in disease controls 5/40 [X[2] =19.2, p<0.001]. AKA gives weaker sensitivity than RF [55.7%], but stronger specificity [87.5% versus other rheumatic, and 92% versus healthy controls]. The frequency of AKA positivity was higher among patients who had severe disease [being positive in 41/50 of active RA patients], this gives a highly significant association p<0.001. Also, AKA shows significant positive association with RF+ve results [45/71]. Combined results of both AKA and RF gave overall best results as both positive results gave a sensitivity of 97.7%, and both negative results gave a specificity of 97.5% versus rheumatic and 98% versus healthy controls. AKA adds a valuable diagnostic tool in the diagnosis of RA. It is more specific than RF. Its positivity is associated with active RA disease. Combined AKA and RF measurement gives the best sensitivity and specificity for diagnosing rheumatoid disease than each test individually

Serum and synovial fluid levels of MMP-3 and TIMP-1 in rheumatoid arthritis and osteoarthritis

Matrix metalloproteinases [MMPs] are cytokine-modulated enzymes that play an important role in the pathogenesis of RA by inducing bone resorption and cartilage destruction. Tissue inhibitors of metalloproteinases [TIMPs] are naturally occurring MMPs inhibitors. In rheumatoid arthritis [RA], there is a disturbed balance between MMPs and TIMPs favoring proteolysis. This study was performed to evaluate the significance of measuring the serum and synovial fluid [SF] levels of MMP-3 and TIMPs in RA and osteoarthritis [OA] patients in an attempt to provide more insight in their role in the pathogenesis of those two diseases. Serum levels of MMP-3 and TIMP-1 were measured from 30 RA, 20 OA patients and 20 healthy controls using double-antibody ELISA. Also, their levels were measured in the SF of 14 RA and 9 OA patients. RA disease activity was assessed using the Multivariate Analysis of Mallya and Mace and joint erosions were assessed using Larsen score. Serum and SF levels of MMP-3 and TIMP-1 were significantly higher in RA than OA patients and in OA patients than controls. Their levels were significantly higher in the SF than in the serum. Serum and SF TIMP-1: MMP-3 ratio was significantly lower in RA as compared to OA patients and normal controls and this ratio was significantly lower in the SF than in the serum of RA patients. Serum levels of MMP-3 and TIMP-1 correlated strongly with clinical and laboratory parameters of rheumatoid disease activity, and the serum levels of MMP-3 showed a significant positive correlation with the number of joint erosions but TIMP-1 levels did not show this positive correlation. Serum and SF MMP-3 and TIMP-1 levels were significantly higher in RA than OA patients and normal controls. They appear to play a critical role in joint inflammation and destruction, especially MMP-3, which may serve as an additional marker for assessment of RA disease activity and severity